Since the initial discovery of LHRH 20 years ago, roughly 5,000 LHRH analogs have been synthesized and evaluated for possible therapeutic use. However, no treatment method for male pattern baldness utilizing LHRH analogs has heretofore been advanced. The present invention is directed to the treatment of male pattern baldness with therapeutic agents known as LHRH analogs.
Male-pattern baldness, also called androgenic alopecia, is largely the result of heredity, advancing age and male hormone secretion, specifically the hormone, dihydrotestosterone. Hence, male-pattern baldness may be said to be a time dependent steroid genetic expression resulting in a diminution in the growing phase of scalp hair. In advanced stages, male-pattern baldness is characterized by a bald scalp at the crown of the head and a horseshoe shaped fringe of hair remaining on the sides of the head.
Various preparations have heretofore been proposed for the treatment of male-pattern baldness. However, these hair growth formulations are not very effective.
Minoxidil, a potent anti-hypertensive medication, has been used with limited success to regrow hair by rubbing it in lotion form into the scalp. One theory for its mode of action is that it dilates the blood vessels in order to stimulate nourishment of hair follicles. Minoxidil is not effective for the treatment of male-pattern baldness because it does not reduce the production of hormones responsible for causing male-pattern baldness. The most common side effects associated with this medication are itching and skin irritation. Moreover, Minoxidil in topical application is poorly absorbed.
Minoxidil is also inconvenient to use because patients receiving Minoxidil treatment for male pattern baldness typically must apply liquid formulations of Minoxidil to the scalp several times each day. The liquid must then be allowed to remain on the scalp for at least four hours after each application and the hair may not be washed until after the foregoing time period has elapsed. Moreover, the patient's hair must be mussed during application of Minoxidil, which does not give the patient a cosmetically pleasing appearance.
Another approach described in U.S. Pat. No. 5,183,817 is to utilize retinoids or mixtures thereof in combination with minoxidil and/or minoxidil-type compounds in stimulating or increasing the rate at which hair grows on mammalian skin. Such treatment does not reduce hormone production. It may produce itching and skin irritation. Moreover, this approach is inconvenient as it requires mussing of the hair.
Still another approach for treating male-pattern baldness has been the topical application of agents which inhibit the conversion of testosterone to dihydrotestosterone. Testosterone binds specifically to the 5.alpha.-reductase enzyme which converts testosterone to its active metabolite dihydrotestosterone (DHT). DHT eventually binds to nuclear receptor proteins and results in the synthesis of specific proteins which lead to male-pattern baldness. U.S. Pat. No. 5,053,403 discloses a method for treating male-pattern baldness through the topical application of an inhibitor of the conversion of testosterone to dihydrotestosterone by the 5.alpha.-reductase enzyme and a blocking agent which blocks the binding of dihydrotestosterone to receptor protein in cell cytoplasm. The disadvantages associated with this method are itching upon topical application, poor absorption, inconvenience in application, and the necessity of mussing of the hair. Furthermore, progesterone and progesterone-like compounds are cited as preferred inhibitors in U.S. Pat. No. 5,053,403. However, because progesterone and progesterone-like compounds do not completely inhibit the conversion of testosterone to dihydrotestosterone, such agents do not provide suitable hair growth.
An orally administered inhibitor of 5.alpha.-reductase currently in clinical trial for the treatment of male-pattern baldness is finasteride, a synthetic 4-azasteroid compound, sold under the name Proscar.RTM.. Finasteride is structurally similar to progesterone. Proscar.RTM. has been used to shrink enlarged prostates by blocking the formation of DHT. However, Proscar.RTM. does not provide an efficacious treatment of male-pattern baldness because it does not sufficiently block DHT production at the intracellular level.
Still another approach to treating male-pattern baldness has been the administration of estrogen or estrogen-based compounds, such as those disclosed in U.S. Pat. No. 5,204,337 issued to Labrie. However, the use of estrogen and estrogen-like compounds for the treatment of male-pattern baldness has not been successful because they place patients at an increased and unacceptable risk of death from cardiovascular complications, such as heart attacks, strokes, and venous thrombosis. Estrogen-like compounds also produce other undesirable side effects, such as unwanted feminization of men. This transsexual effect manifests itself in gynecomastia (enlargement of breasts) and fluid retention. Moreover, estrogen-like compounds and LHRH analogs are structurally dissimilar. Estrogen-like compounds, such as those disclosed in U.S. Pat. No. 5,204,337 have a cyclic-based structure and do not contain amino acid. By contrast, LHRH analogs are characterized by their decapeptide-based structure and contain amino acids. The LHRH analogs of the present invention are non-steroidal and do not produce the undesirable side effects associated with steroids.
The present invention provides treatments for persons suffering from male-pattern baldness which overcome the disadvantages associated with prior methods.